FDA Removes Black Box Warning for Breast Cancer and Other Indications on HRT Products

The FDA has removed a black box warning from hormonal replacement therapy products indicated for menopause which included cardiovascular diseases, breast cancer, and potential dementia, according to a press release from the FDA.¹

The updated labeling will impact the 4 categories of hormone replacement therapy products: estrogen and progesterone, systemic estrogen-alone therapy, systemic progestogen-alone therapy for women with a uterus using systemic estrogen, and topical vaginal estrogen therapy.

“This decision reflects our commitment to follow the science wherever it leads and to correct course when the evidence demands it,” Robert F. Kennedy, Jr, Secretary of Health and Human Services, said in the press release. “By removing these boxed warnings, we ensure that women receive accurate information about hormone therapy—free from exaggeration or fear. A health care system worthy of public trust tells the truth, updates its guidance as science evolves, and respects women’s ability to make informed choices about their own health.”

The decision to remove the black box warning comes after a long road for these products. In January 2003, the FDA implemented class-wide labeling changes for agents involving estrogen-alone and combined estrogen-progestogen products that were approved for menopausal symptoms and osteoporosis.²

This decision stemmed from results from the 2002 Women's Health Initiative Randomized Controlled Trial, where major clinical outcomes were reported with HRs for coronary heart disease, 1.29 (95% CI, 1.02-1.63) with 286 cases; breast cancer, 1.26 (95% CI, 1.00-1.59) with 290 cases; stroke, 1.41 (95% CI, 1.07-1.85) with 212 cases; pulmonary embolism, 2.13 (95% CI, 1.39-3.25) with 101 cases; colorectal cancer, 0.63 (95% CI, 0.43-0.92) with 112 cases; endometrial cancer, 0.83 (95% CI, 0.47-1.47) with 47 cases; hip fracture, 0.66 (95% CI, 0.45-0.98) with 106 cases; and death due to other causes, 0.92 (95% CI, 0.74-1.14) with 331 cases.³ Additionally, the composite outcomes were 1.22 (95% CI, 1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (95% CI, 0.90-1.17) for total cancer, 0.76 (95% CI, 0.69-0.85) for combined fractures, 0.98 (95% CI, 0.82-1.18) for total mortality, and 1.15 (95% CI, 1.03-1.28) for the global index.

In July 2025, an expert panel of Menopause and Hormone Replacement Therapy for Women was hosted by the FDA.⁴ The goal of the meeting was to focus on the risk/benefits of these therapies, including the potential risks of breast cancer, uterine cancer, and certain cardiovascular risks versus potential benefits on bone, genitourinary, cardiovascular, and cognitive health. The panel also focused on the results from the Women’s Health Imitative study, and spoke about the risks/benefits on the age of hormone initiation, formulation, and dose.

This led to the November 2025 decision where the US Department of Health and Human Services and the FDA announced the removal of the black box warnings, which went into effect in February 2026.⁵

“Tragically, tens of millions of women have been denied the life-changing and long-term health benefits of hormone replacement therapy because of a medical dogma rooted in a distortion of risk,” said Marty Makary, MD, MPH, the FDA Commissioner. “For too long, issues of women’s health have been underrecognized. Women and their physicians should make decisions based on data, not fear.”

The February 2026 FDA press release noted that women who initiate hormone replacement therapy within 10 years from the beginning of menopause, particularly before age 60, saw a reduction in all-cause mortality and fractures. However, as of 2020, there were 41 million women in the US who were aged 45 to 64 years, and approximately 2 million women in that group were receiving hormone replacement therapy.

“With today’s action, we are delivering on our promise to make sure women have accurate, scientifically grounded information about the potentially life-changing benefits of HRT,” Makary concluded. “Women face symptoms of menopause that can last for years, and our efforts will help these women make well-informed medical decisions.”

References

1. FDA approves labeling changes to menopausal hormone therapy products. News release. February 12, 2026. Accessed February 16, 2026. https://tinyurl.com/b2evsjc7
2. Makary MA, Nguyen CP, Høeg TB, Tidmarsh GF. Updated labeling for menopausal hormone therapy. JAMA. 2026;335(2):117-118. doi:10.1001/jama.2025.22259
3. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002;288(3):321-333. doi:10.1001/jama.288.3.321
4. FDA expert panel on menopause and hormone replacement therapy for women. News release. July 17, 2025. Accessed February 16, 2026. https://tinyurl.com/bdzayssw
5. HHS advances women’s health, removes misleading FDA warnings on hormone replacement therapy. News release. November 10, 2025. Accessed February 16, 2026. https://tinyurl.com/2yyfh76j